DSpace at VNU: (ReO)-O-V and (ReNPh)-N-V complexes with pentadentate benzamidines - Synthesis, structural characterization and DFT evaluation of isomeric complexes

DSpace at VNU: (ReO)-O-V and (ReNPh)-N-V complexes with pentadentate benzamidines - Synthesis, structural characterizati...

Accepted Manuscript ReVO and ReVNPh Complexes with Pentadentate Benzamidines – Synthesis, Structural Characterization and DFT Evaluation of Isomeric Complexes Hung Huy Nguyen, Pham Chien Thang, Ulrich Abram PII: DOI: Reference: S0277-5387(15)00434-9 http://dx.doi.org/10.1016/j.poly.2015.07.079 POLY 11465 To appear in: Polyhedron Received Date: Accepted Date: 28 June 2015 31 July 2015 Please cite this article as: H Huy Nguyen, P Chien Thang, U Abram, ReVO and ReVNPh Complexes with Pentadentate Benzamidines – Synthesis, Structural Characterization and DFT Evaluation of Isomeric Complexes, Polyhedron (2015), doi: http://dx.doi.org/10.1016/j.poly.2015.07.079 This is a PDF file of an unedited manuscript that has been accepted for publication As a service to our customers we are providing this early version of the manuscript The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain ReVO and ReVNPh Complexes with Pentadentate Benzamidines – Synthesis, Structural Characterization and DFT Evaluation of Isomeric Complexes Hung Huy Nguyen,a)* Pham Chien Thang,b) Ulrich Abramb)* a) Department of Chemistry, Hanoi University of Science, 19 Le Thanh Tong, Hanoi, Vietnam b) Freie Universität Berlin, Institute of Chemistry and Biochemistry, Fabeckstr 34-36, D- 14195 Berlin, Germany Abstract Novel, potentially pentadentate ligands (H3L) for an optimal coordination of {MVO}3+ and {MV(NPh)}3+ cores (M = Re, Tc) have been tailored by a computer-aided procedure They can be prepared by reactions of 2-aminobenzyliminodiacetic acid diethylester with N,N-[(dialkylamino)(thiocarbonyl)]benzimidoyl chlorides and subsequent hydrolysis The ligands react with [ReOCl3(PPh3 )2] or [Re(NPh)Cl3(PPh3)2] under triple deprotonation and form compounds of the general compositions [ReO(L)] and [Re(NPh)(L)], respectively The organic ligands occupy the remaining five coordination positions of the {ReO}3+ and {Re(NPh)}3+ cores in all compounds studied The phenylimido complexes hydrolyze in basic media under formation of their oxidorhenium(V) analogs Keywords: Rhenium, Pentadentate ligands, Oxido complexes, Imido complexes, X-ray structure, DFT Corresponding Autors: nguyenhunghuy@hus.edu.vn (Hung Huy Nguyen) ulrich.abram@fu-berlin.de (Ulrich Abram) 1 Introduction Beside several other applications, rhenium compounds currently attract interest because of potential applications of complexes of the isotopes 186Re and 188 Re in radiotherapy [1-6] Additionally, coordination compounds of rhenium are frequently used as non-radioactive models for development of technetium radiopharmaceuticals [7] In this context, there is a permanent need for efficient chelating systems, which form stable and/or kinetically inert complexes with rhenium or technetium [8] Such a robust coordination sphere is a ‘chemical pre-requisite’ for resisting the competition of other potential ligand systems, which are present in all biological fluids in a huge amount and will meet them on their way to the target organ Pentadentate ligands should be ideal chelators for the stabilization of the frequently formed {ReO} 3+ 3+ core and its analogous phenylimido {ReNPh} core Nevertheless, hitherto there is only a limited number of structurally well-characterized rhenium or technetium complexes with pentadentate ligands reported and particularly such compounds were not in the focus of related nuclearmedical research [9-13] This may possibly be understood by the fact that the syntheses of pentadentate ligands are frequently related to multi-step procedures, which are too time-consuming for the preparation of only one single molecule with uncertain biodistribution features In the light of another strategy, which focuses on the synthesis of a ‘bioconjugation kit’ [14], however, any effort in the synthesis of a robust ‘multi-use ligand’ seems to be justified Following this approach, first 99m Tc or 186,188Re complexes with a strong chelator (having an anchor group in its periphery) are produced This pre-formed radioactive label can then be coupled in a second step with arbitrary peptide-based biomolecules Recently, we reported about such a pentadentate ligand system based on thiocarbamoylbenzamidines, which provides an anchor for the coupling of peptides, and its rhenium and technetium complexes (H3L* and [M(L*)] in Scheme 1) [14] Such multidentate ligands can be prepared from benzimidoyl chlorides and functionalized primary amines [14-17] Scheme Pentadentate benzamidines and their ReO complexes In the present work, we report about the syntheses of similar pentadentate dialkylamino(thiocarbonyl)benzamidines (H3L 3+ Morph Et , and H3L ), which are expected to form 3+ more stable complexes with {ReO} and {ReNPh} cores Results and Discussion 2.1 Computational Studies In order to optimize the coordination abilities of the pentadentate benzamidines by a further increase of the stability of the formed chelates, we searched for alternative ligands With regard to the time-consuming syntheses, we decided to estimate the potential of another promising candidate of a pentadentate ligand (H3L) first by DFT calculations [18] H3L* and H3L are related ligand systems They provide the same donor atom constellations, but with a replaced CH2 spacer in their backbone (Scheme 1) Thus, we calculated the over- all energies for optimized geometries of the diethyl derivatives [ReO(L*Et)] and [ReO(LEt)] The results of the geometrical optimization obtained for [ReO(L*Et)] can directly be compared with the X-ray data of the compound, which are contained contained in ref 14 The optimized parameters are in good agreement with the experimental ones The bond lengths differ by less than 0.04 Å, whereas the angles by o or less A Table with details of the experimental and calculated structural data is contained in the Supplementary Material On the basis of the good agreement between the experimental and calculated data for [ReO(L*Et)], we extended the calculations to the complex [ReO(LEt)] in order to estimate stabilizing or destabilizing effects due to the modifications in the coordination sphere of the metal A comparison of the energies of optimized structures of the two structural isomers [ReO(L*Et)] and [ReO(LEt)] strongly suggests that the latter compound is more stable by a Table Energies of optimized geometries of [ReO(LEt)] and [ReO(L*Et)] at different levels of DFT Basis sets DFT E (Hartree) ∆E[a] method [ReO(LEt)] [ReO(L* Et)] kJ/mol LANL2DZ 6-31G* PBE0 B3LYP -1961.73297 -1963.57025 -1961.72425 -1963.56175 -22.89 -22.31 LANL2DZ 6-31G** PBE0 B3LYP -1961.76982 -1963.60699 -1961.76122 -1963.59860 -22.57 -22.04 LANL2TZ PBE0 B3LYP -1961.79351 -1963.63174 -1961.78475 -1963.62318 -22.99 -22.46 Re C,H,N,O,S 6-31G** [a] ∆E = E[ReO(L)] – E[ReO(L*)] value of about 22 – 23 kJ/mol This energetic difference is nearly independent of the employed DFT methods as well as of the basis set combinations (Table 1) These facts together with the slight discrepancy between the experimental and optimized bonding parameters in [ReO(L*Et) underlines the reliability of performed DFT calculations and encouraged us to undertake the syntheses of ligands of the type H3 L and their rhenium complexes 2.2 Ligand Synthesis Ligands of the type H3L have been obtained in multistep syntheses from 2-nitrobenzylamine as is shown in Scheme In the first step, 2-nitrobenzylamine reacts with an excess of bromoacetic acid ethylester in dry MeCN under reflux and in the presence of a base like K2CO3 The reaction is catalyzed by solid KI, which activates the bromoacetic acid ethylester This iodide-catalyzed coupling proceeds sufficiently fast for the synthesis of The disubstituted product is formed almost quantitatively within 10 h when an excess of 25% bromoacetic acid ethylester is used It should be mentioned that a similar procedure with aromatic amines requires more drastic conditions [14] Scheme The synthesis of the pentadentate ligand H3L The reduction of the nitro group of can be performed either by H2 gas with a Pd/C catalyst or with Raney nickel in an ethylacetate/methanol mixture The first reaction must be quenched after h in order to minimize the formation of side-products due to the cleavage of the N-benzyl bond and gives an overall yield of 55% after purification by column chromatography (silica gel) with ethyl acetate/n-hexane (1:1) More effective is the use of the Raney nickel The reduction proceeds slowly but is much cleaner under the same conditions After 24 h, the reaction is complete and no side-products can be detected by NMR spectroscopy The final ligands H3L are best prepared by reactions of with the corresponding benzimidoyl chlorides to form and subsequent hydrolysis of these compounds with NaOH in methanol Neutralization of the products of such reactions with citric acid gives the pentadendate ligands H3L in high yields An alternative route, which contains the hydrolysis of the ester in the first step produces a number side products due to the low solubility of the dicarboxylic acid in non-alcoholic solvents such as THF or acetone, which are normally used for preparation of benzamidine ligands [14,19,20] The IR spectra of H3L show strong, broad bands for the νOH stretches in the region between 3500 cm-1 and 2500 cm-1 Very strong absorptions around 1720 cm-1 are assigned to νC=O vibrations, which are well separated from the strong absorptions of the ν C=N stretches in the 1616 cm-1 region [21-24] The 1H NMR spectra of H3L are characterized by two singlets around 3.45 ppm and 4.00 ppm, which are assigned to the methylene protons of NCH2CO and PhCH2N, respectively Broad singlets at 9.40 ppm and 11.50 ppm belong to NH and COOH resonances The hindered rotation around the CS-NR1R2 bonds, which is found for many thiocarbamoylbenzamidines, is also observed for H3L This results in magnetic inequality of the two residues R, and consequently the 1H NMR spectrum of H3LMorph shows two overlapping signals with complex coupling patterns of two NCH2 groups and two OCH2 groups of the morpholine residue In the case of H3LEt, two set of well resolved signals corresponding two ethyl groups of -NEt2 residue are observed The +ESI mass spectra of the ligands show clear patterns with expected molecular ion [M+H]+ peaks and confirm their composition unambiguously 2.3 Oxidorhenium(V) complexes Representatives of the novel ligand system H3L react with the sparingly soluble starting material [ReOCl3(PPh3)2] in MeOH/CH2Cl2 under formation of red crystalline solids of the composition [ReO(L)] (4) in high yields (Scheme 3) The reactions are slow at ambient temperature, but can be accelerated by the addition of a supporting base such as Et3N and Scheme Reaction of H3L with [ReOCl3(PPh3)2] heating The products are readily soluble in DMSO or DMF, less soluble in CH2 Cl2 or CHCl3 and almost insoluble in alcohols The IR spectra of show no bands of OH or NH stretches, which reflects the presence of the triply deprotonated forms of the ligands Additionally, the shift of the νC=N band from about 1615 cm-1 in the spectra of the uncoordinated compounds to the region around 1535 cm-1 indicates the formation of a benzamidinate chelate ring Two different absorptions of ν C=O stretches are observed around 1713 cm-1 and 1696 cm-1 and can be assigned to the two nonequivalent carboxylate groups in the molecules The presence of Re=O bonds is confirmed by strong absorptions at 964 cm-1 for 4Morph and at 962 cm-1 for 4Et They appear in the expected range for octahedral ReVO complexes with trans O=Re-O arrangement [7,25,26] The 1H NMR spectra of in DMSO-d are characterized by three pairs of doublets with typical geminal coupling constants corresponding to the protons of three methylene groups in the chelate rings While the two PhCH2N protons resonate at 3.65 and 3.71 ppm, the resonances of the four COCH2N protons appear in the range between 4.6 ppm to 5.6 ppm The rigid structure of NR1R2 residues in corresponding thiocarbamoylbenzamidine complexes has previously been reported and is also observed in [14,25] In the 1H NMR spectrum of 4Morph, four signals, two broadened doublets at 3.89 ppm and 3.97 ppm and another two overlapped in a multiplet at 3.84 ppm, corresponding to the four NCH2 protons are observed Those of the four OCH2 protons give two broadened doublets at 4.30 and 4.51 ppm and a multiplet at 4.58 ppm Similarly, the rigid structure of NEt2 results in four magnetically unequalent CH2 protons, which correspond to four well-resolved double quartets with a geminal coupling constant of J1 = 14 Hz and a vicinal coupling constant of J2 = 7.0 Hz The 1H NMR spectra of recorded in DMSO-d are quite different from those recorded in CDCl3 with respect to the chemical shift of the NR1R2 residues and the CH2 protons in the chelate rings In the case of complex 4Morph, the spectrum in CDCl3 shows an overlapped multiplet at 3.92 ppm, which is assigned to four NCH2 protons, and two well separated multiplets at 4.22 ppm, 4.36 ppm and one overlapping multiplet at 4.51 ppm, which are assigned to the four OCH2 protons in the morpholinyl residue Figure depicts the molecular structure of 4Morph Some important bond lengths and angles are summarized in Table The rhenium atom has adopted a distorted octahedral Figure Molecular structure of [ReO(LMorph)] (4Morph) [32] Hydrogen atoms are omitted for clarity coordination environment, in which five positions of the coordination sphere are occupied by the donor atoms of the ligand {LMorph}3- and the remaining position is occupied by a terminal oxido ligand The molecular structure of 4Morph confirms the presence of the triply deprotonated form of the organic ligand One of the carboxylic groups (O68) is in trans position to the oxido ligand, while O64 occupies a cis position This is consistent with the two C=O bands observed in the IR spectrum of 4Morph The Re-O68 bond length is slightly shorter than the Re-O64 distance, reflecting some transfer of electron density from the rhenium oxygen double bond to this bond [26,27] The partial double bond character of the C4–N5 bond may make the six-membered chelate ring containing the aminobenzylamine Table Selected experimental bond lengths (Å) and angles (deg) in [ReO(LMorph)] (4Morph) Re–O10 1.672(7) Re–O64 2.055(7) C62–O63 1.20(1) Re–S1 2.309(2) Re–O68 2.040(7) C62–O64 1.32(1) Re–N5 2.037(8) S1–C2 1.76(1) C66–O67 1.22(1) Re–N8 2.207(7) C4–N5 1.35(1) C66–O68 1.29(1) O10–Re– S1 103.4(2) O10–Re–O64 94.8(3) N5–Re–O64 166.2(3) O10–Re–N5 95.8(3) O10–Re–O68 164.4(3) S1–Re–N5 94.6(2) O10–Re–N8 88.2(3) S1–Re–N8 165.4(2) N8–Re–N5 93.0(3) unit rigid and, thus, it is prevented from switching between boat and chair conformation as is suggested by the splitting of PhCH2N signals of the ring in the 1H-NMR spectrum of the compound 2.3 Phenylimidorhenium(V) complexes with H3L The rhenium(V) phenylimido core, which is isoelectronic with the rhenium(V) oxido core, is expectedly also stabilized by the H3L chelator system However, reactions of H3L with Experimental 4.1 Materials All chemicals used in this study were reagent grade and used without further purification Solvents were dried and used freshly distilled unless otherwise stated [ReOCl3(PPh3)2] and [Re(NPh)Cl3(PPh 3)2] were prepared by standard procedures [28,29] The syntheses of the N,N-[(diethylamino)(thiocarbonyl)]benzimidoyl chloride and [(morpholinyl)(thiocarbonyl)]benzimidoyl chloride were performed by the procedure of Beyer et al [30] 4.2 Physical Measurements Infrared spectra were measured as KBr pellets on a Shimadzu FTIR-spectrometer between -1 400 and 4000 cm NMR spectra were taken with JEOL 400 MHz and Bruker 500 MHz multinuclear spectrometers Positive ESI mass spectra were measured with an Agilent 6210 ESI-TOF (Agilent Technology) mass spectrometer All MS results are given in the form: m/z, assignment Elemental analysis of carbon, hydrogen, nitrogen and sulfur were determined using a Heraeus vario EL elemental analyzer 4.3 Syntheses of the ligands 4.3.1 2-Nitrobenzyliminodiacetic acid diethylester (1) 2-Nitrobenzylamine (6.086 g, 40 mmol), ethyl bromoacetate (11.0 mL, 99 mmol), a mixture of finely powdered K2CO3 (16.8 g, 122 mmol), KI (1.0 g) and 100 mL of dry MeCN were heated under reflux for 10 h After being cooled to room temperature, the mixture was filtered and the solvent was removed under reduced pressure The excess of ethyl bromoacetate was removed by heating the mixture to 80oC under a pressure of about 20 mmHg The product was obtained as a slightly yellow oil Yield 96 % (12.45 g) Elemental analysis: Calcd for C15H20N2O6: C, 55.55; H, 6.22; N, 8.64% Found: C, 55.36; H, 6.31; N, 8.51% 1H NMR (400 MHz, CDCl3, ppm): 1.25 (t, J = 7.1 Hz, 6H, CH2CH3), 13 3.55 (s, 4H, NCH2CO), 4.17 (q, 7.1 Hz, 4H, CH2CH3), 4.26 (s, 2H, PhCH2N), 7.41-7.87 (m, 4H, aromat H) 4.3.2 2-Aminobenzyliminodiacetic acid diethylester (2) A mixture of compound (4.865 g, 15 mmol), Raney nickel (® 3202 Sigma Aldrich, about g), MeOH (30 mL) and ethyl acetate (5 mL) was stirred under an atmosphere of hydrogen at room temperature for 24 h The reaction mixture was filtered and the organic solvents were completely removed under vacuum to give the product in almost quantitative yields as a yellow oil Elemental analysis: Calcd for C15H22N2O4: C, 61.21; H, 7.53; N, 9.52% Found: C, 61.01; H, 7.46; N, 9.49% H NMR (400 MHz, CDCl3, ppm): 1.27 (t, J = 7.1 Hz, 6H, OCH2CH3), 3.47 (s, 4H, CH2CO), 3.85 (s, 2H, PhCH2N), 4.16 (q, 7.1 Hz, 4H, OCH2CH3), 6.62- 7.09 (m, 4H, aromat H) 4.3.3 N,N-Dialkylaminothiocarbonyl-N’-{phenylene-(2-methyliminodiacetic acid diethylester)} benzamidines (3) Solid benzimidoyl chloride (5.0 mmol) was added to a mixture of (1.47 g, 5.0 mmol) and triethylamine (1,51 g, 15 mmol) in 20 mL of dry THF The mixture was stirred for h at room temperature The formed precipitate of NEt3 · HCl was filtered off and the filtrate was evaporated under reduced pressure to dryness The residue was washed with diethyl ether (20 mL) and dried in vacuum to give as yellow solids 3Morph: Yield 90% (2.304 g) Elemental analysis: Calcd for C27H34N4O5S: C, 61.5; H, 6.5; N, 10.6; S, 6.1% Found: C, 61.0; H, 6.3; N, 10.4; S, 6.2% IR (KBr, cm-1): 3248 (br, s), 2949 (w), 2875 (w), 1756 (s), 1724 (s), 1629 (s), 1539 (s), 1481 (m), 1450(m), 1183 (m), 1091 (m), 1024 (m), 756 (s) H NMR (500 MHz, CDCl3, ppm): 1.25 (t, J = 7.0 Hz, 6H, 14 OCH2CH3), 3.50 (s, 4H, NCH2CO), 3.72 (m, 4H, NCH2), 3.98 (q, J = 7.0 Hz, 4H, OCH2CH3), 4.05 (s, br, 2H, PhCH2N), 4.11 (m, 4H, OCH2), 6.95-7.77 (m, 9H, aromat H), + 10.23 (s, 1H, NH) +ESI MS (CH2Cl2): 527.2 (100% base peak, [M+H] ); 559.2 (20% base peak, [M+Na]+) 3Et: Yield 90% (2.304 g) Elemental analysis: Calcd for C27H36N4O4S: C, 63.2; H, 7.1; N, -1 10.9; S, 6.3% Found: C, 63.0; H, 7.2; N, 10.7; S, 6.4% IR (KBr, cm ): 3267 (br, s), 2978 (w), 2935 (w), 1751 (s), 1726 (s), 1630 (s), 1537 (s), 1489 (m), 1452(m), 1193 (m), 1080 (m), 1024 (m), 754 (s) 1H NMR (500 MHz, CDCl3, ppm): 1.18 (t, br, 6H, NCH2CH3), 1.24 (t, J = 7.0 Hz, 6H, OCH2CH3), 3.50 (s, 4H, NCH2CO), 3.69 (t, J = 7.0 Hz, 2H, NCH2CH3), 3.95 (t, J = 7.0 Hz, 2H, NCH2CH3), 4.00 (q, J = 7.0 Hz, 4H, OCH2CH3), 4.03 (s, br, 2H, PhCH2N), 6.98-7.79 (m, 9H, aromat H), 10.15 (s, 1H, NH) +ESI MS (CH2Cl2): 513.2 (100% base peak, [M+H]+); 535.2 (30% base peak, [M+Na]+); 551.2 (5% base peak, [M+K]+) 4.3.4 N,N-Dialkylaminothiocarbonyl-N’-{phenylene-(2-methyliminodiacetic acid)} benzamidines (H3 L) NaOH (50 mmol) was added to a solution of compound (4.0 mmol) in MeOH (20 mL) and the reaction mixture was stirred overnight After reducing the volume to about mL, 20 mL of brine and citric acid monohydrate (1.05 g, 50 mmol) were added The resulting suspension was extracted twice with portions of 20 mL THF The organic phases were combined and evaporated to dryness The raw products were dissolved in CH2Cl2/MeOH (1/1, v/v) and recrystallized by slow evaporation of such solutions H3LMorph: Yield 84% (1.574 g) Elemental analysis: Calcd for C23H26N4O5S: C, 58.7; H, 5.6; - N, 11.9; S, 6.8% Found: C, 58.4; H, 5.6; N, 12.3; S, 6.7% IR (KBr, cm 1): 3201 (br, s), 1720 (br, s), 1616 (s), 1527 (s), 1450 (m), 1427 (s), 1277 (s), 1227 (s), 1110 (s), 1026 (m), 764 (m), 698 (m) 1H NMR (400 MHz, CDCl3, ppm): 3.44 (s, 4H, NCH2CO), 3.66 (m, 4H, NCH2), 3.86 15 (m, 4H, OCH2), 4.02 (s, 2H, PhCH2N), 6.93- 7.48 (m, 9H, aromat H), 9.38 (s, 1H, NH), + 11.45 (s, br, 2H, COOH) +ESI MS (CH2Cl2): 471.2 (100% base peak, [M+H] ); 493.1 (65% base peak, [M+Na] +) H3LEt: Yield 81% (1.482 g) Elemental analysis: Calcd for C23H28N4O4S: C, 60.5; H, 6.2; N, 12.3; S, 7.0% Found: C, 60.1; H, 6.2; N, 12.5; S, 6.9% IR (KBr, cm-1): 3214 (br, s), 1718 (br, s), 1615 (s), 1530 (s), 1457 (m), 1450(s), 1272 (s), 1122 (s), 1095 (s), 1026 (m), 770 (m), 697 (m) H NMR (400 MHz, CDCl3, ppm): 1.09 (t, J = 7.0 Hz, 3H, NCH2CH3), 1.13 (t, J = 7.0 Hz, 3H, NCH2CH3), 3.45 (s, 4H, NCH2CO), 3.60 (t, J = 7.0 Hz, 2H, NCH2CH3), 3.71 (t, J = 7.0 Hz, 2H, NCH2CH3), 4.04 (s, br, 2H, PhCH2N), 6.90-7.6 (m, 9H, aromat H), 9.36 (s, 1H, NH), 11.51 (s, br, 2H, COOH) +ESI MS (CH2Cl2): 457.1 (35% base peak, + + [M+H] ); 479.2 (100% base peak, [M+Na] ) 4.3.5 [ReO(L)] (4) H3L (0.1 mmol) in mL of MeOH and drops of Et3N were added to a stirred solution of [ReOCl3(PPh 3)2] (83.2 mg, 0.1 mmol) in mL CH2Cl2 The reaction mixture was heated under reflux for 30 After being cooled to room temperature, the reaction mixture was slowly evaporated, which resulted in the precipitation of the red crystalline complexes The products were filtered off and recrystallized from CH2Cl2/MeOH Reactions of equimolar amounts of H3L and (NBu4)[ReOCl4] in MeOH result in the same products, but with slightly lower yields [ReO(LMorph)] (4Morph) Yield 70% (46.9 mg) Elemental analysis: Calcd for C23H23N4O6SRe: C, 41.2; H, 3.5; N, 8.4; S, 4.8% Found: C, 41.2; H, 3.3; N, 8.3; S, 4.8% IR - (KBr, cm 1): 3050 (w), 2962 (w), 2934 (w), 1713 (vs), 1696 (vs), 1535 (s), 1481 (m), 1434 (m), 1296 (m), 1226 (w), 1119 (m) 964 (m), 933 (m), 910 (m), 771 (m), 717 (w) 1H NMR (500 MHz, DMSO-d6, ppm): 3.65 (d, J = 18.5 Hz, 1H, PhCH2N), 3.72 (d, J = 18.5 Hz, 1H, PhCH2N), 3.84 (m, br 2H, NCH2), 3.89 (d, br 1H, NCH2), 3.97 (d, br, 1H, NCH2), 4.30(d, 16 br, 1H, OCH2), 4.51 (d, br, 1H, OCH2), 4.58 (m, br, 2H, OCH2), 4.63 (d, J = 15.0 Hz, 1H, NCH2CO), 4.97 (d, J = 15.0 Hz, 1H, CH2CO), 5.47 (d, J = 12.5 Hz, 1H, NCH2CO), 5.58 (d, J 13 = 12.5 Hz, 1H, NCH2CO), 6.84-7.59 (m, 9H, aromat H) C NMR (DMSO-d6, ppm): 50.86, 50.93 (NCH2), 61.64 (PhCH2N), 66.68, 66.72 (OCH2), 68.06, 68.78 (NCH2CO), 125.58, 126.65, 128.11, 128.87, 130.71, 131.64, 132.20, 133.98, 135.97(Caromat.), 152.73 (Caromat.-N), 168.50 (C=N), 173.68, (C=O), 175.17 (C=O), 182.32 (C=S) +ESI MS (CH2Cl2): 671.2 + (100% base peak, [M+H] ) [ReO(LEt)] (4Et): Yield 74% (48.0 mg) Elemental analysis: Calcd for C23H25N4O5SRe: C, 42.1; H, 3.8; N, 8.5; S, 4.9% Found: C, 42.3; H, 3.6; N, 8.3; S, 4.7% IR (KBr, cm-1): 3055 (w), 2938 (w), 1712 ( vs), 1695 (vs), 1533 (s), 1475 (m), 1297 (m), 1121 (m) 962 (m), 931 (m), 775 (m) H NMR (500 MHz, DMSO-d6, ppm): 1.39 (t, (t, J = 7.0 Hz, 3H, NCH2CH3), 1.46 (t, (t, J = 7.0 Hz, 3H, NCH2CH3), 3.66 (d, J = 18.0 Hz, 1H, PhCH2N), 3.71 (d, J = 18.0 Hz, 1H, PhCH2N), 4.04 (dq, J1 = 14.0 Hz, J2 = 7.0 Hz, 1H, NCH2CH3), 4.08 (dq, J1 = 14.0 Hz, J2 = 7.0 Hz, 1H, NCH2CH3), 4.25 (dq, J1 = 14.0 Hz, J2 = 7.0 Hz, 1H, NCH2CH3), 4.57 (dq, J1 = 14.0 Hz, J2 = 7.0 Hz, 1H, NCH2CH3), 4.64 (d, J = 15.0 Hz, 1H, NCH2CO), 4.96 (d, J = 15.0 Hz, 1H, NCH2CO), 5.47 (d, J = 12.5 Hz, 1H, NCH2CO), 5.59 (d, J = 12.5 Hz, 1H, NCH2CO), 6.75-7.57 13 (m, 9H, aromat H) C NMR (DMSO-d6, ppm): 13.95, 14.02 (NCH2CH3), 48.46, 48.71 (NCH2CH3), 61.69 (PhCH2N), 68.09, 68.82 (NCH2CO), 125.46, 126.73, 127.79, 129.07, 130.85, 131.47, 132.22, 134.08, 135.88(Caromat.), 152.79 (Caromat.-N), 167.64 (C=N), 173.20, (C=O), 175.00 (C=O), 182.38 (C=S) +ESI MS (CH2Cl2): 657.1 (45% base peak, [M+H]+); + + 679.1 (100% base peak, [M+Na] ); 695.2 (80% base peak, [M+K] ) 4.3.6 [Re(NPh)(L)] (5) H3L (0.1 mmol) and drops of Et3N were added to a stirred suspension of [Re(NPh)Cl3(PPh3)2] (90 mg, 0.1 mmol) in mL of CH2Cl2 The reaction mixture was heated on reflux for hour During this time, the precursor complex completely dissolved and a clear 17 yellow-green solution was obtained The solvent was removed under vacuum and the residue was purified by column chromatography on silica with a CHCl3/n-hexane mixture (1:1, v/v) as mobile phase [Re(NPh)(LMorph)] (5Morph): Yield 40% (29.0 mg) Elemental analysis: Calcd for C29H28N5O5ReS: C, 46.7; H, 3.8; N, 9.4; S, 4.3% Found: C, 46.5; H, 3.6; N, 9.2; S, 4.5% IR - (KBr, cm 1): 3060 (w), 2990 (w), 2900 (w), 2858 (w), 1701 (vs), 1508 (s), 1481 (s), 1435 (s), 1342 (m), 1299 (m), 1261 (m), 1219 (m), 1110 (m), 1022 (m), 914 (w), 899 (w), 806 (m), 771 (m), 732 (w), 682 (w), 528 (w) 1H NMR (400 MHz, CDCl3, ppm): 3.48 (d, J = 17.1 Hz, 1H, PhCH2N), 3.73 (d, J = 17.1 Hz, 1H, PhCH2N), 3.89 (m, 4H, NCH2), 4.23 (d, J = 14.6 Hz, 1H, CH2CO), 4.30 (m, 2H, OCH2), 4.49 (m, 2H, OCH2), 4.82 (d, J = 14.6 Hz, 1H, CH2CO), 5.03 (d, J = 12.1 Hz, 1H, CH2CO), 5.27 (d, J = 12.1 Hz, 1H, CH2CO), 6.65-7.47 (m, 14H, 13 aromat H) C NMR (CDCl3, ppm): 49.61, 49,83 (NCH2), 61.85 (PhCH2N), 66.53, 66.79 (OCH2), 69.67, 69.99 (NCH2CO), 122.16, 124.22, 124.37, 128.24, 128.63, 128.67, 130.11, 130.99, 131.28, 131.45, 132.90, 136.76(Caromat.), 152.62 (Caromat.-N), 156.34 (Caromat.-N=Re), 166.85 (C=N), 174.39, (C=O), 176.97 (C=O), 181.88 (C=S) +ESI MS (CH2Cl2): 746.1 (100% base peak, [M+H]+); 768.2 (70% base peak, [M+Na]+) 4.4 X-Ray Crystallography The intensities for the X-ray determinations were collected on a STOE IPDS 2T instrument with Mo Kα radiation (λ = 0.71073 Å) Standard procedures were applied for data reduction and absorption correction Structure solution and refinement were performed with SHELXS97 and SHELXL97 [31] Hydrogen atom positions were calculated for idealized positions and treated with the ‘riding model’ option of SHELXL More details on data collections and structure calculations are contained in Table 18 Table X-ray structure data collection and refinement parameters [ReO(LMorph)] [Re(NPh)(LMorph)] Formula C23H23N4O6ReS C29H28N5O5ReS Mw 669.71 744.82 Crystal system Monoclinic Orthorhombic a/ Å 9.562(1) 7.813(1) b/ Å 22.684(1) 8.565(1) c/ Å 0.620(1) 40.864(3) α/o 90 90 β/ 94.25(1) 90 γ/o 90 90 V/ Å3 2297.4(3) 2734.3(4) Space group P21/n P 212121 Z 4 1.936 1.809 µ/mm 5.429 4.571 No of reflections 13961 14880 No of independent 4871 6831 Rint 0.0936 0.0997 No parameters 317 371 R1/wR2 0.0439 / 0.0834 0.0515 / 0.1122 GOF 1.003 0.882 o -3 Dcalc./g cm -1 Flack parameter -0.030(18) 4.5 Computational details Et Et The gas phase geometries of [ReO(L )] and [ReO(L* )] were optimized without any symmetry restrictions in singlet ground states by the DFT method with two different exchange correlation functional approaches, PBE1PBE and B3LYP, using the Gaussian-09 Revision D.01 program package [18] For the complex [ReO(L* Et)], the initial geometry 19 used for the optimization is based on crystal structure parameters [14] Regarding to the Et Et complex [ReO(L )], the initial geometry is derived from crystal structure of [ReO(L* )] with modification of position of CH2 group, and because the single crystal suitable for Xray structure analysis was not available, the significant bond lengths and angles of the optimized geometry are compared with the crystal structure of 4Morph The employed basis set combinations are found in Table The basis set LANL2TZ for Re was obtained from the EMSL Basis Set Library [33,34] The optimized geometries were verified by performing frequency calculations The absence of an imaginary frequency ensures that the optimized geometries correspond to true energy minima Energy values for both complexes were corrected by Zero Point Energy (ZPE) All theoretical calculations were carried out with the high-performance computing system of ZEDAT, Freie Universität Berlin, (https://www.zedat.fu-berlin.de/HPC/Home ) Acknowledgements We gratefully acknowledge financial support from DAAD (Deutscher Akademischer Austauschdienst, Germany) Appendix A Supplementary data CCDC-1400143 and CCDC-1400144 contain the supplementary crystallographic data for [ReO(LMorph)] and [Re(NPh)(LMorph)], respectively These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223336-033; or e-mail: deposit@ccdc.cam.ac.uk References [1] E W Price, C Orvig, Chem Soc Rev 43 (2014) 260 20 [2] C S Cutler, H M Hennkens, N Sisay, S Huclier-Markai, S S Jurisson, Chem Rev 113 (2013) 858 [3] C F Ramogida, C Orvig, Chem Commun 49 (2013) 4729 [4] 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S I Khan, M M Abu-Omar, Inorg Chem 40 (2001) 6767 [30] L Beyer, R Widera, Tetrahedron Letters 23 (1982) 1881 [31] G M Sheldrick, Acta Cryst A64 (2008) 112 [32] K Brandenburg, DIAMOND, vers 3.2i, Crystal Impact GbR, Bonn, Germany [33] D Feller, J Compt Chem 17 (1996) 1571 [34] K L Schuchardt, B T Didier, T Elsethagen, L Sun, V Gurumoorthi, J Chase, J Li, T L Windus, J Chem Inf Model 47 (2007) 1045 23 Figure Captions Figure Molecular structure of [ReO(LMorph)] (4 Morph) [32] Hydrogen atoms are omitted for clarity Figure Molecular structure of [Re(NPh)(LMorph)] (5Morph) [32] Hydrogen atoms are omitted for clarity 24 Figure Molecular structure of [ReO(LMorph)] (4 Morph) [32] Hydrogen atoms are omitted for clarity 25 Figure Molecular structure of [Re(NPh)(LMorph)] (5Morph) [32] Hydrogen atoms are omitted for clarity 26 Graphical Abstract A novel family of pentadentate ligands for nuclearmedical procedures has been developed and optimized by a computer-aided procedure The resulting SN2O2 ligands form very stable complexes with {ReO}3+ units 27 ...ReVO and ReVNPh Complexes with Pentadentate Benzamidines – Synthesis, Structural Characterization and DFT Evaluation of Isomeric Complexes Hung Huy Nguyen,a)* Pham... -1 963.57025 -1 961.72425 -1 963.56175 -2 2.89 -2 2.31 LANL2DZ 6-3 1G** PBE0 B3LYP -1 961.76982 -1 963.60699 -1 961.76122 -1 963.59860 -2 2.57 -2 2.04 LANL2TZ PBE0 B3LYP -1 961.79351 -1 963.63174 -1 961.78475 -1 963.62318... ligands With regard to the time-consuming syntheses, we decided to estimate the potential of another promising candidate of a pentadentate ligand (H3L) first by DFT calculations [18] H3L* and